1 -like receptors, immunoglobulins, and mutant
myocilin.
2 Grp94 and reducing its novel client, mutant
myocilin.
3 tions in other OLF family members, including
myocilin.
4 uced expression of wild type, Q368X or P370L
myocilin.
5 M citrate synthase in the presence of 650 nM
myocilin.
6 s to promote the clearance of toxic forms of
myocilin.
7 n anterior chamber exchange with recombinant
myocilin (
2 microg/mL), whereas the fellow eye received
8 Myocilin,
a causative gene for open angle glaucoma, enco
9 promotes the aggregation of mutant forms of
myocilin,
a protein associated with primary open-angle g
10 Mutant
myocilin accumulates in the endoplasmic reticulum for un
11 Tg-MYOC(Y437H) mice, most likely by reducing
myocilin accumulation and ER stress in the TM.
12 proved the secretion of myocilin and reduced
myocilin accumulation as well as endoplasmic reticulum (
13 s, suggesting broader relevance of misfolded
myocilin across the disease spectrum, but the absence of
14 aken together, the interaction of Grp94 with
myocilin aggregates can be manipulated by cellular envir
15 the toxic accumulation of amyloid-containing
myocilin aggregates, hastening the onset of the prevalen
16 Myocilin also affects differentiation of oligodendrocyte
17 Recombinant
myocilin also increased outflow resistance in eyes incub
18 Myocilin also protected GAPDH from thermal inactivation
19 Myocilin also stimulated osteogenic differentiation of w
20 Myocilin also suppresses the thermal aggregation of citr
21 iency virus vector encoding both full-length
myocilin (
amino acids 1-503 fused to C-terminal V5 and s
22 orescence (EF) microscopy with antibodies to
myocilin and alpha smooth muscle (alpha-SMA).
23 as performed in addition to Western blots of
myocilin and alphaB-crystallin.
24 Myocilin and angiopoietin-like 7 expression in response
25 ed by the synergistic interaction of mutated
myocilin and another significant risk factor, oxidative
26 Immunohistochemistry was performed with anti-
myocilin and anti-V5 antibodies.
27 ar meshwork cells differently from wild-type
myocilin and can reduce cell survival.
28 duced reporter gene luciferase or endogenous
myocilin and fibronectin expression were determined.
29 2 interacted with Olfm1 and -3, but not with
myocilin and gliomedin.
30 Treatment of NIH 3T3 cells with
myocilin and its fragments induced intracellular redistr
31 The exact role of
myocilin and its functional association with glaucoma ar
32 To study the functions of human
myocilin and its two proteolytic fragments, these protei
33 Myocilin and optineurin are two genes linked to glaucoma
34 ects of force-expressed wild-type and mutant
myocilin and optineurin on neurite outgrowth in neuronal
35 ells with pEGFP-N1 (mock control) as well as
myocilin and optineurin plasmids including pMYOC(WT)-EGF
36 pOPTN(WT)-EGFP and pOPTN(E50K)-EGFP nor the
myocilin and optineurin small-interfering RNA treatments
37 ts demonstrated that the two glaucoma genes,
myocilin and optineurin, exhibited differential effects
38 udies were performed with antibodies against
myocilin and other ECM components, including fibronectin
39 PBA significantly improved the secretion of
myocilin and reduced myocilin accumulation as well as en
40 mal regions, of which the gene MYOC encoding
myocilin and the gene OPTN encoding optineurin have been
41 Myocilin and the heparin II domain of fibronectin also i
42 , gain-of-function association between human
myocilin and the peroxisomal targeting signal type 1 rec
43 used to determine the protein expression of
myocilin and TIMP-1 in conditioned media collected from
44 Quantitative PCR for
myocilin and versican isoforms was performed in addition
45 Myocilin and Wnt proteins may perform redundant function
46 actomedin 1 (Olfm1), olfactomedin 3 (Olfm3),
myocilin,
and gliomedin was studied by using co-immunopr
47 beta-galactosidase (TAT-HA-beta-gal), TAT-HA-
myocilin,
and TAT-HA-myocilin-EGFP.
48 in structure, function, and pathogenesis for
myocilin;
and offers insights into highly conserved, bio
49 eted protein, acidic, cysteine rich (SPARC),
myocilin,
angiopoietin-like factor (ANGPTL)-7, and trans
50 Mutated
myocilin appears to affect trabecular meshwork cells dif
51 Recombinant
myocilin appears to form a complex in porcine aqueous hu
52 Recombinant
myocilin appears to form a complex in porcine aqueous hu
53 It is known that some mutations in the gene
myocilin are associated with POAG.
54 Functions of
myocilin are poorly understood.
55 However, the functions of wild-type
myocilin are still not well understood.
56 f myocilin was blocked by antibodies against
myocilin,
as well as secreted inhibitors of Wnt signalin
57 cues glaucoma phenotypes in a mouse model of
myocilin-
associated glaucoma (Tg-MYOC(Y437H) mice).
58 Our results indicate that
myocilin-
associated glaucoma is an ER storage disease an
59 Myocilin at 18 nM was more effective than 1 muM bovine s
60 phin-associated protein complex (DAPC), as a
myocilin-
binding candidate.
61 Myocilin binds to ErbB2/ErbB3, activates these receptors
62 f efficiently handling the removal of mutant
myocilin,
but when Grp94 is depleted, degradation of mut
63 Induction of
myocilin by dexamethasone was observed in conditioned me
64 ed protein (Grp) 94 depletion reduces mutant
myocilin by engaging autophagy.
65 Studies were conducted to see whether
myocilin can act as a general molecular chaperone.
66 glaucoma, but the mechanism by which mutant
myocilins cause disease is poorly understood.
67 The Y437H mutant
myocilin cell line also produced more reactive oxygen sp
68 The Y437H mutant
myocilin cell line showed the highest sensitivity to the
69 enes were down-regulated in the Y437H mutant
myocilin cell line, but not in other cell lines.
70 mide gel electrophoresis was used to analyze
myocilin complex formation in porcine aqueous humor.
71 urite length in those cells transfected with
myocilin constructs was shortened and the number of neur
72 Myocilin-
containing conditioned medium also increased pr
73 We further determined whether
myocilin contributes to GC-OHT.
74 Thus, strategies aimed at eliminating
myocilin could be therapeutically relevant for glaucoma.
75 In addition,
myocilin-
deficient mesenchymal stem cells exhibited redu
76 Grp94-selective inhibitor facilitated mutant
myocilin degradation and rescued phenotypes in a transge
77 metastasis model as well as enhanced mutant
myocilin degradation in a glaucoma model compared to BnI
78 oss the disease spectrum, but the absence of
myocilin does not cause disease.
79 T in humans, and we further demonstrate that
myocilin does not play a major role in DEX-induced OHT i
80 Transduction of myocilin or
myocilin-
EGFP was evaluated by immunostaining or fluores
81 AT-HA-beta-gal), TAT-HA-myocilin, and TAT-HA-
myocilin-
EGFP.
82 Levels of extracellular
myocilin expressed by TM cells were increased in respons
83 Full-length mutant
myocilin expressed in mammalian cells forms intracellula
84 nd compared gene expression profiles between
myocilin-
expressing and vector control cell lines by a m
85 e) polymerase, were significantly reduced in
myocilin-
expressing cells as compared with control cells
86 eam kinases, c-Raf and MEK, was increased in
myocilin-
expressing cells compared with control cells.
87 raction of differentially expressed genes in
myocilin-
expressing cells was associated with cell growt
88 Increased proliferation of
myocilin-
expressing cells was demonstrated by the WST-1
89 Myocilin-
expressing cells were more resistant to serum s
90 Conditioned medium from
myocilin-
expressing cells, as well as purified myocilin,
91 ascorbic acid to DMEM-AH failed to increase
myocilin expression beyond that obtained with DMEM-AH.
92 Dex-induced
myocilin expression had both cytosolic and extracellular
93 CR analysis revealed significant decrease in
myocilin expression in eyes receiving AA compared to nai
94 Wild-type mice showed increased
myocilin expression in the TM on DEX-Ac treatment.
95 GC-induced
myocilin expression in the trabecular meshwork (TM) has
96 In vitro quantitative assays of
myocilin expression in TM cells can be used for characte
97 The
myocilin expression is known to be up-regulated by gluco
98 eutic doses of BOL-303242-X elicit a reduced
myocilin expression profile in TM cells by virtue of the
99 Myocilin expression was also analyzed by Western immunob
100 In DMEM-AH-conditioned medium,
myocilin expression was increased and TIMP-1 expression
101 Myocilin expression was investigated in a subset of eyes
102 cross-linked actin networks and induction of
myocilin expression.
103 h human MSCs exhibiting the highest level of
myocilin expression.
104 rpose of this investigation was to elucidate
myocilin function(s).
105 nto adipocytes, and treatment with exogenous
myocilin further enhanced osteogenesis.
106 Mutations in the
myocilin gene (MYOC) are the most common known genetic c
107 Mutations in the
myocilin gene are associated with juvenile and adult-ons
108 Mutations of the
myocilin gene are one cause of autosomal dominant juveni
109 tively common promoter region variant in the
myocilin gene for which there is a commercially availabl
110 We sequenced the
myocilin gene in probands from each family and found mut
111 human pathology related to mutations in the
MYOCILIN gene is primary open-angle glaucoma.
112 It is well documented that mutations in the
MYOCILIN gene may lead to juvenile- and adult-onset prim
113 Mutations in the
MYOCILIN gene may lead to juvenile- and adult-onset prim
114 ately 10%-20% are caused by mutations in the
myocilin gene.
115 and referred by their eye practitioner, and
Myocilin genetic testing was performed by direct sequenc
116 The levels of wild type and mutant
myocilin-
GFP in various clones were confirmed by Western
117 ressing wild type or mutant (Q368X or P370L)
myocilin-
GFP upon Dox induction, are valuable in facilit
118 high expression of wild type, Q368X or P370L
myocilin-
GFP upon doxycycline (Dox) induction were obtai
119 Genetically,
myocilin glaucoma follows autosomal dominant, recessive
120 POAG caused by DCV at MYOC has been termed "
myocilin glaucoma".
121 al for patients suffering from some cases of
myocilin glaucoma.
122 Expression of human
myocilin glaucomatous mutations in mouse eyes causes ele
123 line-inducible (Tet-on) wild type and mutant
myocilin-
green fluorescence protein (GFP) expressing RGC
124 These results demonstrate that
myocilin has a de-adhesive activity and triggers signali
125 Wild-type (WT)
myocilin has been associated with steroid-induced glauco
126 Aggregation of wild-type
myocilin has been reported in other glaucoma subtypes, s
127 Elevated levels and aggregation of
myocilin hasten increased intraocular pressure and glauc
128 th steroid-induced glaucoma, and variants of
myocilin have been linked to early-onset inherited glauc
129 tial of MSCs and may identify a new role for
myocilin in bone formation and/or maintenance in vivo.
130 inhibition are possible mechanisms by which
myocilin in overabundance may lead to TM cell or tissue
131 Recombinant
myocilin in porcine aqueous humor increased outflow resi
132 h induced expression of wild type and mutant
myocilin in RGC5 cell lines.
133 H) mice by promoting the secretion of mutant
myocilin in the aqueous humor and by decreasing intracel
134 Analysis of the
myocilin in the aqueous humor and TM revealed that PBA s
135 These data implicate a role for
myocilin in the development and/or maintenance of myelin
136 by decreasing intracellular accumulation of
myocilin in the ER, thus preventing TM cell death.
137 Overexpression of
myocilin in the eye angle tissues of transgenic mice sti
138 equivalent levels of mutated human or mouse
myocilin in the eyes of transgenic mice produce comparab
139 aB-crystallin levels remained unchanged, but
myocilin in the HTM cells was decreased in some samples.
140 The expression of
myocilin in the iridocorneal angle tissues and aqueous h
141 mmunohistochemistry revealed the presence of
myocilin in the juxtacanalicular region of the trabecula
142 Expression of 15-fold higher levels of
myocilin in the muscles of transgenic mice led to the el
143 Accumulation of Y437H
myocilin in the TM induced endoplasmic reticulum stress
144 y be valuable in studies of proteins such as
myocilin in the TM.
145 transgenic mice expressed elevated levels of
myocilin in tissues of the iridocorneal angle.
146 intracellular accumulation of mutant and WT
myocilin in vitro, cell culture, and model organisms, th
147 of Grp94 promotes the degradation of mutant
myocilin in vitro, to date no Grp94-selective inhibitors
148 With some HTM cells,
myocilin increased to a greater extent when untreated ce
149 onstruct, but not with that of the wild-type
myocilin,
increased the apoptotic activity in cells.
150 ining was also noted in TM tissues of TAT-HA-
myocilin-
incubated or -perfused eyes.
151 TM cell cultures, after TAT-HA-
myocilin incubation, showed an enhanced myocilin stainin
152 Expression of mutated
myocilin induced its intracellular accumulation and prev
153 ocilin-expressing cells, as well as purified
myocilin,
induced the formation of stress fibers in prim
154 Myocilin-
induced elongation of oligodendrocyte processes
155 However, the pathogenic mechanisms of
myocilin-
induced glaucoma are still largely unknown.
156 ciferase reporter activity, fibronectin, and
myocilin induction in TM cells.
157 Myocilin induction was assessed after exposure of TM cel
158 Myocilin interacted with alpha1-syntrophin via its N-ter
159 There,
myocilin interacts with gliomedin, neurofascin, and NrCA
160 nted secretion of both mutated and wild-type
myocilin into the aqueous humor.
161 Myocilin is a gene linked directly to juvenile- and adul
162 Myocilin is a gene linked to the most common form of gla
163 Here we demonstrate that
myocilin is a mediator of oligodendrocyte differentiatio
164 Myocilin is a protein found in the extracellular matrix
165 Myocilin is a protein found in the trabecular meshwork e
166 Myocilin is a secreted glycoprotein that belongs to a fa
167 Myocilin is a secreted glycoprotein that is expressed in
168 Although
myocilin is detected in several ocular and nonocular tis
169 In cells, when wild-type
myocilin is driven to misfold and aggregate, it becomes
170 Myocilin is expressed and secreted by optic nerve astroc
171 Here we report that
myocilin is expressed in bone marrow-derived mesenchymal
172 We demonstrate that in sciatic nerve,
myocilin is expressed in Schwann cells with high concent
173 Myocilin is induced in response to several cellular stre
174 Although
myocilin is not abundantly expressed in rat eye angle, o
175 In HTM cells, Pro370Leu mutant
myocilin is not secreted under normal culture conditions
176 hen Grp94 is depleted, degradation of mutant
myocilin is shunted away from ERAD toward a more robust
177 Myocilin is thought to be a stress response protein, but
178 Myocilin is typically transported through the ER/Golgi n
179 The glaucoma-associated gene,
myocilin,
is expressed in ocular and non-ocular tissues
180 ER/Golgi network, but inherited mutations in
myocilin lead to its misfolding and aggregation within t
181 hronic expression of misfolded, non-secreted
myocilin leads to HTM cell death, trabecular meshwork dy
182 Expression of two mutant
myocilins led to different levels of endoplasmic reticul
183 glucocorticoids in TM cells, and an altered
myocilin level may be the culprit in conditions such as
184 tions of the anterior segment, and comparing
myocilin levels in the aqueous humor and trabecular mesh
185 dent antagonism to drug-induced increases in
myocilin levels.
186 fibrils in aggregated forms of WT and mutant
myocilin localized to the C-terminal olfactomedin (OLF)
187 One function of
myocilin may be to serve as a molecular chaperone.
188 cell growth and cell death, suggesting that
myocilin may have a role in the regulation of cell growt
189 Mutant
myocilins may confer different sensitivity to oxidative
190 r results suggest that expression of mutated
myocilins may have a sensitization effect, which can lea
191 undant functions in the mammalian eye, since
myocilin modulates Wnt signaling by interacting with com
192 uced greater or similar amounts of SPARC and
myocilin mRNA after Lat-B treatment.
193 Myocilin mRNA and protein levels increased when HTM cell
194 SPARC and
myocilin mRNA expression were dramatically increased on
195 h surfaces, suggesting that the reduction of
myocilin mRNA when cells are plated onto flat tissue cul
196 8-month-old transgenic mice expressing Y437H
myocilin mutant.
197 We have found that disease-causing
myocilin mutants are misfolded, are highly aggregation-p
198 genesis investigations of disease-associated
myocilin mutants.
199 r relatives of participants found to carry a
Myocilin mutation.
200 for JOAG, we used families that did not have
myocilin mutations for a genomewide screen.
201 This is the first study to report
Myocilin mutations in an advanced POAG cohort.
202 The prevalence of
Myocilin mutations in glaucoma cases with severe visual
203 Prevalence and spectrum of
Myocilin mutations in individuals with advanced and nona
204 Identifying individuals who have
Myocilin mutations provides an opportunity to screen at-
205 The prevalence of
Myocilin mutations rose from 16% to 40% in selected adva
206 Exon 3
Myocilin mutations were identified in 45 advanced POAG p
207 No pathogenic
Myocilin mutations were identified in exons 1 and 2 in e
208 Twenty-six individuals with
Myocilin mutations were identified through cascade genet
209 ome a novel treatment for POAG patients with
myocilin mutations.
210 Mutations in
myocilin (
MYOC) are the most common genetic cause of pri
211 y open-angle glaucoma (POAG) patients with a
Myocilin (
MYOC) disease-causing variant who presented th
212 Myocilin (
MYOC) dominant gain-of-function mutations have
213 Sequence variations in the
myocilin (
MYOC) gene account for approximately 2% to 4%
214 on into a BAC carrying the full-length human
MYOCILIN (
MYOC) gene and long flanking regions.
215 Mutations in the
myocilin (
MYOC) gene are the most common genetic factors
216 Specific mutations in the
myocilin (
MYOC) gene cause primary open angle glaucoma (
217 ngle glaucoma by expression of mutated mouse
myocilin (
Myoc) in transgenic (Tg) mice.
218 Myocilin (
MYOC) is a protein with a broad expression pat
219 assettes were knocked into the 3'-UTR of the
Myocilin (
Myoc) locus, an abundantly expressed extracell
220 ies of wild-type and mutated mouse and human
myocilin (
Myoc) proteins as a prerequisite for developme
221 collected for Western immunoblot analysis of
myocilin (
MYOC).
222 e glaucoma-associated olfactomedin domain of
myocilin (
myoc-OLF) is a recent addition to the growing
223 lved crystal structures of the OLF domain of
myocilin (
myoc-OLF), the best studied such domain to dat
224 rotein folding, promotes secretion of mutant
myocilin,
normalizes cell morphology and reverses cell l
225 Sciatic nerves of
myocilin null mice express reduced levels of several mye
226 lin sheath thickness of optic nerve axons in
Myocilin-
null mice compared with wild-type littermates,
227 Optic nerves of
Myocilin-
null mice contain reduced levels of several mye
228 f optic nerve oligodendrocytes is delayed in
Myocilin-
null mice.
229 amined the calcium binding properties of the
myocilin OLF domain (myoc-OLF).
230 rp94 recognizes on-pathway aggregates of the
myocilin olfactomedin domain (myoc-OLF), accelerates rat
231 Similar to its family member
myocilin,
Olfm1 is stabilized by calcium.
232 -B dramatically downregulated both SPARC and
myocilin on 75 kPa hydrogels.
233 Stronger
myocilin or HA staining was also noted in TM tissues of
234 Transduction of
myocilin or myocilin-EGFP was evaluated by immunostainin
235 Assays further revealed that upon
myocilin overexpression, the activity of RhoA was dimini
236 EX and PRED significantly increased cellular
myocilin (
P < 0.0001), while GW870086X did neither.
237 l migration was consistent with demonstrated
myocilin phenotypes including the loss of actin stress f
238 Myocilin physically interacts with Lingo-1 and may be co
239 We suggest that intracellular
myocilin plays a role as a regulator of muscle hypertrop
240 These results suggest that
myocilin promotes cell proliferation and resistance to a
241 Myocilin protected citrate synthase activity against the
242 C(50)s for PA were higher than DEX, for both
myocilin protein and mRNA.
243 Myocilin protein did not affect actin polymerization.
244 SPARC and
myocilin protein expression paralleled changes in mRNA e
245 hibitor reduced the levels of several mutant
myocilin proteins as well as wild-type myocilin when for
246 s performed to determine whether full-length
myocilin purified from a human trabecular meshwork cell
247 dy by the authors has shown that recombinant
myocilin purified from a prokaryotic expression system i
248 Myocilin purified from human trabecular meshwork cells i
249 These results indicate that aberrant
myocilin quaternary structure drives Grp94 recognition,
250 Expression of
myocilin rose during the course of human MSC differentia
251 Myocilin screening in phenotypically selected cases can
252 All three GCs increased fibronectin and
myocilin secretion in a concentration-dependent manner (
253 el SEGRA GW870086X increases fibronectin and
myocilin secretion similar to two traditional GCs, effec
254 These data suggest that
myocilin should be considered as a target for improving
255 Myocilin signaling through ErbB2/3 receptors may contrib
256 Myocilin significantly reduced thermal aggregation of ci
257 The selected mRNAs (IL-6, IL-8,
myocilin,
SPARC [secreted protein, acidic and rich in cy
258 The mRNAs of
myocilin,
SPARC, and MMP-3, which do not have AREs, were
259 T-HA-myocilin incubation, showed an enhanced
myocilin staining compared with the control cultures.
260 isolated dorsal root ganglion cultures with
myocilin stimulates clustering of the nodal proteins neu
261 Myocilin stimulation of oligodendrocyte differentiation
262 facilitating folding and secretion of mutant
myocilin suggest a new type of treatment for this form o
263 nhibitor also facilitate clearance of mutant
myocilin,
suggesting that therapeutic approaches aimed a
264 Grp94 triages mutant
myocilin through ER-associated degradation, subverting a
265 rk-inducible glucocorticoid response protein/
myocilin (
TIGR/MYOC) are associated with juvenile glauco
266 lar expression and secretion of fibronectin,
myocilin,
tissue plasminogen activator (tPA), and/or mat
267 Genetic studies have linked
myocilin to open angle glaucoma, but the functions of th
268 The addition of mutant
myocilin to the short list of Grp94 clients strengthens
269 oprecipitation experiments and by binding of
myocilin to the surface of cells expressing cysteine-ric
270 This inhibitor rescued mutant
myocilin toxicity in primary human trabecular meshwork c
271 Human and bovine TM tissues after TAT-
myocilin transduction also exhibited a diminished actin
272 Myocilin transduction resulted in a loss of actin stress
273 Myocilin transfectants displayed a heightened sensitivit
274 nectin protein and mRNA were also reduced in
myocilin transfectants.
275 ibers and increased trypsin sensitivity from
myocilin transfection could be reverted by co-expression
276 ct on neurite outgrowth was also elicited by
myocilin transfection in RGC5 cells.
277 partially rescued by exogenous extracellular
myocilin treatment.
278 n 90 (Hsp90), specifically recognizes mutant
myocilin,
triaging it through ERAD.
279 ably transfected HEK293 cell line expressing
myocilin under an inducible promoter and compared gene e
280 essing wild-type or mutant (Y437H and I477N)
myocilins under an inducible promoter.
281 Inherited, disease-causing
myocilin variants aggregate intracellularly instead of b
282 Both wild-type and certain
myocilin variants containing mutations in the olfactomed
283 Stress fiber-inducing activity of
myocilin was blocked by antibodies against myocilin, as
284 Expression of
myocilin was detected in MSCs derived from mouse, rat, a
285 ound up was reduced when wild type or mutant
myocilin was expressed.
286 Myocilin was isolated and purified from porcine trabecul
287 Mutant
myocilin was not secreted into the aqueous humor but acc
288 DMEM-FBS (442%), but only a 10% increase in
myocilin was observed beyond the normal induction in DME
289 tance in eyes incubated in DMEM, but only if
myocilin was preincubated with porcine aqueous humor (78
290 er the secreted, glaucoma-associated protein
myocilin was processed by this pathway.
291 Recombinant
myocilin was purified from the media using nickel ion af
292 All three exons of
myocilin were bidirectionally sequenced.
293 Increased mRNA and protein levels of
myocilin were observed when cells were grown on 400-nm p
294 enic mice expressing 6-fold higher levels of
myocilin when compared with their wild-type littermates.
295 utant myocilin proteins as well as wild-type
myocilin when forced to misfold in cells.
296 Wild type
myocilin,
when transfected into cultured human TM cells,
297 Myocilin,
which is abundant in human eye angle tissues,
298 The codistribution of
myocilin with ECM components was also investigated.
299 Double labeling of
myocilin with other ECM components was performed with di
300 Interaction of
myocilin with sFRP1, sFRP3, and several Frizzled recepto